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1943-1946 (Undergraduate Notes, Box 2)

The next one is a fairly straightforward tutorial in which I was asked to write an essay on the hypothalamus. I don’t know that it’s anything particularly notable, but I fulfilled by obligation and wrote it. Then we go on to other things that are obviously physiological. The next package that we came across is again a tutorial with David Whitteridge, “What do you understand by localization of function in the cerebral cortex?” A very interesting topic and I remember thinking how interesting it was to this day, as most observers of the central nervous system I’m sure would agree.

The next package really should probably have been looked at in relation to the pain one, because it’s just notes on Adrien’s work on century changes in single cutaneous nerve fibers. No, it’s in relation to nerve conduction which I’d been interested in. These are just notes, they’re not any particular insights from me, I’m just making notes on what I was reading.

This next package is something that I wouldn’t have any idea how to answer now. It’s “what differences in postural activity are shown in the thalamic and decerebrate animal?” and evidently at the time I thought I knew something about it, because I start off by “an analysis of posture, followed by a consideration of the various centers and influences removed on decerebration and in making a thalamic preparation enable us well to see the differences in these two animals, as regards postural activity.” It sounds very learned but I don’t think it was.

“What are the chemical factors controlling respiration and what are their modes of action?” And it’s not a very long tutorial as it were, I have I think about 14 page or thereabouts, which for me was fairly short. And then there’s a collection of a lot of the notes that were taken to try to understand that.

The last one in this series is evidently an essay, it’s called “essay 3,” so I presume there are essays 1 and 2 but I haven’t been able to find them, so they probably don’t exist anymore. But essay 3 was again an essay, almost certainly for Whitteridge, “it has been found clinically that there is a limit to the rate of the infusion of blood of normal and exsanguinous patients, what experiments would you perform to elucidate this point?” Interesting topic because it actually has some relevance to my own history. I had a kidney stone, a very small one, at one time, and had the usual procedures, and then after the procedure I was given an infusion of saline. But the people who set up the infusion set it up at a very high rate, which my wife noticed and just commented on, and about halfway through the night then I had quite severe problems of cardiac failure as a result of over-infusion rate of saline into a person, which can happen even if the person is completely well and normal. If you’re infused too fast, you cause trouble, and that’s what this essay was about.

Continuing the general topics was a weekly tutorial on the anterior lobe of the pituitary, and no particular question asked in this case, but it was the interaction of the hypothalamus and the pituitary. It starts off with this sentence: “if owing to the close interrelation of the hypothalamus and neighboring brain tissues with the pituitary, the interpretation of results of tumors, etc., the hypothalamus is of the hypothesis is often difficult, etc. etc.” But anyway that’s what I was writing about.

This is one of the rather later level layers of the packages that we’ve uncovered. An interesting topic here, physiology again. “How far has the study of simplified systems advanced our ideas of the nature of synaptic transmission in the central nervous system?” Very interesting, because at that time, people hadn’t resolved the question of whether it was electrical or chemical, and of course it’s combination of both. But it was a very interesting topic to me at the time, because as I’ve mentioned elsewhere, I was thinking of the possibility of doing later work on the central nervous system, and synapses would have been quite interesting in that area.

This next group of tutorial essays takes off after essay 3, we’ve got now essay 4, 5, 6, and 7, and so on. So essay 4 was “what are the mechanisms which maintain the blood pressure in the human being at a constant level? What cardiovascular adaptations are there associated with changes in posture?” It’s interesting to me now because quite a lot of my work in the past 10-15 years has been related to the genetic factors which alter blood pressure. And so this is some of the material that in my earlier training gave me the background to understand blood pressure. So, essay 4 is then on the mechanisms which maintain blood pressure constant. And essay 5 is not all that dissimilar a topic, “what important methods have been used to investigate the coordination of the heartbeat?” So this is more emphasizing for me to understand what methods have been used. And I start off by saying they may be arranged in several groups: methods involving pressure changes, investigations of the sound, electrical changes in the heart, etc. So that was an attempt to learn about what methods have been used. Essay number 6 is “What are the variations of blood pressure which occur in the pulmonary circuit compatible with health and light?” So it’s thinking about the pulmonary circulation and that still is a very difficult topic for physiologists and physicians to control the pulmonary blood pressure. And then here we’re talking about the heart and the brain and how their circulations are maintained, because essay number 8 is “what are the factors which normally control the cerebral and coronary circulations?” And it starts off with saying “although the changes in cerebral and coronary circulations which are observed under different conditions are often similar, they’re not primarily interconnected. It’s therefore convenient to treat the two separately.” I don’t know whether I would agree with that anymore, but that’s how it started off.

The next package that I have in front of me is just notes on the Annual Review of Biochemistry 1945 by Kalckar, talking about phosphate compounds and enzymes in carbohydrate metabolism. And that was really – and there’s a whole package of material here — and it really is the material that was behind my being able to write the tutorial which led to my first paper, or my authorship on a paper, by Sandy Ogston that I’ve mentioned several times.

I have here a physiology tutorial, which was on the relation of the cortex and thalamus to sensation. Fairly long dissertation on this topic, goes on for about something like 20 pages or thereabout. Fairly straightforward tutorial. But in the same package there is a couple pages that I have some difficulty in understanding when they were done, because it’s headed “Anatomy” with my name on the right hand side, which usually means that it’s a tutorial, and yet it’s discussing the relationship of the thalamus to sensory experiences. And yet it’s called anatomy rather than physiology. So I imagine it was also with Whitteridge, but just labeled anatomy because that’s the particular topic. There are only 4 pages, but quite nice pages with some pretty colored crayon and drawings that I rather like, even now. So it’s an interesting package. In the same package there are a very considerable number of notes on various things that I read in relation to these topics.

There are two tutorials still on the topic that we’ve seen before, on nerve conduction. One is on the evidence of the core conductor hypothesis, and/or the propagation of the nervous impulse by eddy currents, so this was when people were beginning to understand nerve conduction. I don’t remember whether the importance of nodes was known at that time or not, but its relation to nerve conduction, a topic that was interesting to me when I wrote about it. The second one of the same general topic is a tutorial on the facts and theories relating to the ionic composition of nerve axoplasm, the resting potential, the nerve membrane, and action potential, with a note on the myelin sheath. So it’s written more as if it was notes, but it’s in the form that I associate with giving it as a tutorial. Some notes here in relation to nerve conduction, I’m sure, talking about the unit for sensory reception in the cornea. And it’s talking about Adrien’s technique for isolating afferent fibers and sense organs attached, etc. etc. A rather difficult topic I’m sure, I don’t remember much about it. They’re just notes.

There is a tutorial here that’s on the relation of the pyramidal and extrapyramidal systems to control the voluntary movement and the lower motor neurons. I’m quite fascinated to see the sophistication of topics that one was expected to be able to write about as a student. I don’t know how deep the understanding was but surely the tutors made you try hard because they asked difficult questions.

More notes on the hypothalamus here. The hypothalamus, just notes, from a German article [title in German], I’m sure that’s not the right pronunciation, but that’s what it is. The anatomy and connections and physiology of the hypothalamus.

The next series of papers or notes are obviously from the time when I was doing my second degree after taking the animal physiology course and being exposed to Sandy Ogston and his ideas. I decided that I should take a second degree in chemistry to make sure that I was not handicapped by a failure to understand chemical things. And I joined the course in the second and third year of chemistry and took the first part of the chemical examinations at the end of that time. I never did hear how well I did in those exams. I think it probably was like something that happened to Sandy Ogston (a rather enjoyable account he gave of the idiosyncrasies of the Oxford system) because he took two degrees, he did chemistry first and then physiology second, whereas I did physiology first and chemistry second. And after he did the first degree in physiology – I’m sorry, Sandy Ogston did the first degree in chemistry and got first class honors, and then took the second degree in physiology. And after he completed the exam, he asked the examiners how he’d done and whether he’d got to the standard needed for first class honors, they said “Oh Ogston we didn’t bother to read your exam, we knew that he couldn’t get a standing from the exam.” So he never did find out how he went on. I think probably the same thing happened to me except in the reverse order. That after getting my honors degree, which had to be judged as first class, second class, etc., the chemistry degree couldn’t be graded in that way, and so it was only read very cursorily by the examiners. I never did hear how I did. But anyway the next series of packages are related to being taught chemistry.

So the first one in this group is notes on plant sugars and polymerized compounds from sugar starch and the like. It turned out that later on using starch was a very important part of my – or starch gels – was a very important part of my later work. There is a package on plant sugars and polymerized compounds. One package in which the — evidently a tutorial in this case because it’s headed in the usual way, Chemistry and Smithies on the right — the methods of synthesis of pyrrole, pyridine, quinoline, etc. etc., and so it goes. A package also on some simple alkaloids and related compounds. One on an account of some flower pigments, interestingly enough because that was probably related to what my organic chemistry professor, whose name just escaped me for the moment, was famous for, because he worked out a lot of the structures of flower pigments. He was quite famous.

Some notes on the chemistry that was being taught at the 1931 meeting of the British association. Biarum (?) on solubilities and iron solvent forces, and somewhere else in this collection we have a tutorial I wrote on solubilities that was a topic of some interest to me. A bunch of notes on aromatic character of homocyclics, talking about benzene rain, of course with the 6 carbons, and the 4 carbon structure with a question mark, not known. I think that’s been fairly recently developed with 4 carbon atoms, and it’s fairly highly explosive, the form that’s been used. A modern explosive. Interesting package, I’d like to read it again.

A simple one on copper, silver, and gold. One on the alkaline earth metals, barium, magnesium, calcium, strontium, etc. When I did the chemistry course I was rather careful to emphasize the substances that I was likely to meet in biology. So the calcium, etc., magnesium were all elements that occur in nature. But I didn’t spend much time on the rare earth, etc., because I didn’t realize of course how important they would be in other contexts as they now are. Now a tutorial on the halogens. One on alpha-amino acids, another on the terpenes. Actually I think I got a question on the terpenes in the exams, if I remember correctly, and rather enjoyed answering it. Notes on cholesterol. Vitamin B1. And that’s entertaining because I think I forgot the structure of one of the vitamins and was asked by one of the professors of biochemistry whether – let me try that again. In the practical exam, in the biochemistry part of my physiology degree, one of the examiners who happened to be there was interested in whether I really did know the difference between two vitamins, because I’d written the right formula for one vitamin but labeled it with another vitamin’s name, so I obviously didn’t know which was which. But I seem to remember vitamin B1 was one of those that I got wrong, and here’s my notes on it.

Sulfanilamides, very interesting, because here is amino sulfonamide. Of course these sulfanilamides were the first of the drugs that were developed that were anti-bacterial. Not developed, but discovered to be anti-bacterial. My uncle died of boil infections before the sulfanilamides were available. My sister a year later had highly infected tonsils but sulfanilamides were then available, and she survived and lived to have a good life.

Pyrimidines, purines and pyrimidines, a big thick set of notes on them. Powell, talking about the properties of matter, crystal structure determined by x-ray diffraction, another time when really there was – x-ray diffraction was talked about. Written with some joy as I remember, because the properties of matter was always a topic of great interest to me. Even in high school we had a very good textbook on the properties of matter, which I wish I could find because it was so delightful. Barrow – pages and pages of stuff from Barrow, it won’t all be from Barrow, but it’s all on colloids, pages and pages of it, maybe 30 or 40 pages, on colloids. I don’t remember who Barrow was or why I was particularly interested in him. So this must have been a whole bunch of things of that sort, because here’s one headed just Irving, physical methods of analysis, even bound a little bit, so I must have enjoyed it. Conductivity titrations, another topic; Wolfendon, applications of electromotive force measurements, and finally a bunch of things all together just labeled Wisconsin Symposium, and it talks about various things in relation to more biochemical than chemical topics.

The last series of things are nothing to do with lecture notes or tutorials, but they still have some interest because some of them are the actual exam questions. For example there’s one on the honors school of natural science, the final examination general physical chemistry. So that was when I was taking my chemistry degree, 1948. It was on June 17, my sister’s birthday, 1948. I must have been, what, 23 then? So there’s one on general physical chemistry, one on practical organic chemistry, one on general organic chemistry, and one on advanced organic chemistry. One on advanced physical chemistry, advanced inorganic chemistry, so they had a lot of (?) in relation to it. One on physiology, practical biochemistry, honors school of natural science final examination, general inorganic chemistry, and a final examination in practical inorganic chemistry. So quite interesting to be able to see what topics were being questioned in the exam and what type of exams were being set by the examiners. An example of a question is when you had to answer 5 questions, out of a total number of possible ones of 8, so you couldn’t miss many of them, but I have here the first one which is “explain concisely how the second law of thermodynamics may be applied to obtain results of importance in physical chemistry.” It asks you to calculate the latent heat of fusion of benzene from various things that you’re given. I have a note here: 2,720 calories per mole was my answer. I don’t know whether it was right or wrong but that was my answer.

There was one entertaining exam here that was not printed in the neat form of those honors one. It’s just a typewritten exam, the Theodore Williams scholarship examination. This is now July 1945. So that was when I was doing physiology. And I still remember it actually because there was a list of 8 questions of which you had to answer 4 (or not more than 4 should be answered), and I evidently decided that alright then I’m not going to answer 4, I’m going to answer 3, and the one that I remember to this day is “compare the regenerative capacity of bone, nerve, and muscle.” Actually when I read the list of questions I almost left the – I’ll backtrack a little bit. The Theodore Williams scholarship was of course an exam that would determine whether or not you were elected a Theodore Williams scholar for the year. It was an anatomy prize, but the professor of anatomy was Le Gros Clark, and he was really more interested in cell biology than anatomy as such. So, his questions were not very anatomical in a sense, and I remember that there was one student who knew anatomy backwards and forwards, he could tell you every nerve and every muscle, and everything related to anatomy, and had it been classical anatomy he would have definitely got the prize. In fact I won the prize because of Le Gros Clark’s interpretation of anatomy. And I still remember my answer to question number 3, which was “compare the regenerative capacity of bone, nerve, and muscle” and I actually had quite a nice essay on it, because I found they were much more comparable than one might think, and much depended upon the preservation of the muscle and the tissue surrounding the muscle, or the membrane, I don’t even remember it completely but I do remember enjoying it and anyway I did get the prize.

…Contained about 15 pages of notes, not on ordinary paper, but rather strange. The solubility of solids is what it starts with, and there’s pages and pages of notes and equations and things that I don’t even remember where they came from, or in what relation they were accumulated, but there they are, a whole bunch of pages.

A couple pages looking at ? trying to work out the equations related to the passage of light through a prism. Looks quite neat and fairly sophisticated, but I don’t know what it’s about anymore.

A rather incomplete set of notes on the absorption diet – on the absorption in the gastric, pancreatic, and intestinal enzymes concerned with absorption of proteins. Nitrogen, bowels, and so on. Talking about different substances that might be encountered, must have been in relation to understanding diet.

There are two in a sense manuals dating back to my postdoctoral time in Wisconsin. One of them is describing the procedures for using model 38 of the tiselius electrophoresus apparatus, which I used in some of the work when I was a postdoc in Wisconsin. And notes on the directions for manipulation of the machine. There’s a manual, or rather a set of notes, prepared by LJG and JWW. LJG was Lou Gosting, and JWW was Jack Williams. Lou Gosting was a young professor and Jack Williams was my advisor as a postdoctoral fellow at Wisconsin. There’s a section on the optical methods for following electrophoresis or ??? experiments. And then there is a set of my notes on various topics, talking about antibodies, quite a little bit on antibodies, and there’s some rather impenetrable notes on – completely impenetrable notes on the — I can’t even tell what they are, they’re so impenetrable at this point. They look very sophisticated. I’ll leave them for what they’re worth. And finally copies of the abstract of my thesis, which is saved elsewhere. This work arose from observations made by Ogston and Johnson on the osmotic pressure of solutions of protein mixtures. The observed osmotic pressure’s up to 10% greater than those expected, but their method was not accurate enough, and so I did my PhD on getting a more accurate method. Nobody ever used it, but I enjoyed developing the method.